The Behavioral Pharmacology Unit is directed toward the assessment of pharmacological agents designed to modify the behavioral effects of substance abuse, using monkey self-administration and drug discrimination. Other capabilities have been developed to explore pharmacological properties of CNS-active drugs, in an effort to have access to rodent models to screen effects of agent before testing in primates. The neuroendocrine and immune function in plasma of drug-trained monkeys will be examined in the future, and PET scanning will be utilized before and after exposure to drugs of abuse in order to determine potential changes in various neurotransmitter systems as a consequence of prior drug exposure. These studies are unique in that they will investigate potential differences in animals working for drug, as opposed to simple non- contingent exposure to drug. Previous studies have linked susceptibility to drug abuse with individual differences in susceptibility to stress activation of the hypothalamic pituitary adrenal (HPA) axis. The primary endogenous agents involved in the HPA axis are corticotropin releasing hormone (CRH), adrenocorticotropic hormone and cortisol. Several studies have been directed at examining the behavioral specificity of the direct effects of CRH on behavior. Behavioral effects of beta-carbolines: These drugs exhibit profound behavioral effects, and may possibly serve as a pharmacological model of stress or anxiety. Our results with these drugs suggest that some behavioral effects of inverse agonists may not be strictly opposite those of benzodiazepines. Effects of sigma ligands: Excitatory amino acids, acting at the NMDA receptor, have been postulated to play an important role in the acquisition of behavior (learning). Our data are consistent with the notion that excitatory amino acid blockade prevented the development of a learned emotional response, suggesting a potential role for this receptor in the development of anxiety-related disorders in humans. Behavioral consequences of HIV infection - the role of GP120 in dementia: The effects of recombinant and purified native gp120, the envelope protein of human immunodeficiency virus (HIV), were assessed on the acquisition of a spatial discrimination. It was found that gp120 may induce cognitive impairment in HIV-infected individuals, possibly through the interference of vasoactive intestinal polypeptide-mediated activity in the central nervous system.